Brain-derived neurotrophic factor fails to arrest neuromuscular disorders in the paralysé mouse mutant, a model of motoneuron disease.
Several new neurotrophic factors have been recently identified and shown to prevent motoneuron death in vitro and in vivo. One such agent is brain-derived neurotrophic factor (BDNF). In this study, we tested BDNF on an animal model of early-onset motoneuron disease: the paralysé mouse mutant, characterized by a progressive skeletal muscle atrophy and the loss of 30-35% of spinal lumbar motoneurons between the first and second week post-natal. The results show that subcutaneous injections of 1 or 10 mg/kg BDNF did not have any significant effect in increasing the mean survival time of mutant mice or in preventing the loss of motor function and total body weight in paralysé mice. The weight and choline acetyltransferase activity of specific muscles and the number of motoneurons in the spinal cords were identical in BDNF-treated and placebo-injected paralysé mice. These results suggest that BDNF does not act on the disease process in paralysé mice in the conditions we used. By contrast, BDNF has previously been shown to partially prevent the loss of motor function in the wobbler mouse, a suggested model of later-onset motoneuron disease. Taken together these findings suggest that BDNF acts differently on early and late-onset motoneuron diseases. It is however possible that treatment of paralysé mice with BDNF or combinations of different neurotrophic factors prior to the phenotypical expression of the paralysé mutation may prevent the loss of motor function and motoneurons in mutant mice.
Blondet
B
B
INSERM U 153, Paris, France.
Murawsky
M
M
Houenou
L J
LJ
Li
L
L
Aït-Ikhlef
A
A
Yan
Q
Q
Rieger
F
F
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D051379:Mice; D008818:Mice, Neurologic Mutants; D016472:Motor Neuron Disease / Q000235:genetics* / Q000517:prevention & control*; D009046:Motor Neurons / Q000187:drug effects; D009468:Neuromuscular Diseases / Q000235:genetics* / Q000517:prevention & control*; D010243:Paralysis / Q000235:genetics*; D004856:Postural Balance / Q000187:drug effects; D016019:Survival Analysis
D019208:Brain-Derived Neurotrophic Factor; D002795:Choline O-Acetyltransferase